Chromosomal Abnormalities

Another kind of chromosomal abnormality is alteration of chromosome structure. Structural defects arise during replication of the chromosomes just prior to a meiotic cell division. Meiosis is a complex process that often involves the chromosomes exchanging segments with each other in a process called crossing-over. If the process is faulty, the structure of the chromosomes changes. Sometimes these structural changes are harmless to the zygote; other structural changes, however, can be lethal.

Five types of general structural alterations occur during replication of chromosomes (Figure 3). All four types begin with the breakage of a chromosome during replication. In a deletion, the broken segment of the chromosome is "lost." Deletion can be terminal (arises from one break) or interstitial (arises from 2 breaks). A particular case is the ring chromosome where two points of breakdown are present and then fused. Segment distal to the breaks are lost and sucha alost involves both arms of the chromosome. In isochromosomes one of the chromosome arms (p or q) is duplicated, and all material from the other arm is lost. The arm of one side of the centromere is a mirror image of the other. In a duplication, the segment joins to the other chromosome of the pair. In an inversion, the segment attaches to the original chromosome, but in a reverse position. It can be pericentric (break and rearrangements of both sides of the centromere) or paracentric (break and rearrangment on the same of centromere) In a translocation, the segment attaches to an entirely different chromosome.Translocaton can be Robertsonian (involves chromosomes 13–15, 21, and 22) where the whole arms of these chromosomes named acrocentric are fused and reciprocal. Reciprocal translocation results from breakage and exchange of segments between chromosomes.

Because chromosomal alterations in structure cause the loss or misplacement of genes, the effects of these defects can be quite severe. Deletions are usually fatal to a zygote. Duplications, inversions, and translocations can cause serious defects, as the expression of the gene changes due to its changed position on the chromosomes.

Examples of structural chromosomal abnormalities include cri du chat syndrome. Cri du chat means "cat cry" in French. Children with this syndrome have an abnormally developed larynx that makes their cry sound like the mewing of a cat in distress. They also have a small head, misshapen ears, and a rounded face, as well as other systemic defects. These children usually die in infancy. Cri du chat is caused by a deletion of a segment of DNA in chromosome 5.

A structural abnormality in chromosome 21 occurs in about 4% of people with Down syndrome. In this abnormality, a translocation, a piece of chromosome 21 breaks off during meiosis of the egg or sperm cell and attaches to chromosome 13, 14, or 22.

Some structural chromosomal abnormalities have been implicated in certain cancers. For instance, myel-ogenous leukemia is a cancer of the white blood cells. Researchers have found that the cancerous cells contain a translocation of chromosome 22, in which a broken segment switches places with the tip of chromosome 9.

Some unusual chromosomal abnormalities include Prader-Willi syndrome, Angelman's syndrome, and Fragile X syndrome. These structural defects are unusual because the severity or type of symptoms associated with the defect depend on whether the child receives the defect from the mother or the father.

Both Prader-Willi syndrome and Angelman's syndrome are caused by a deletion in chromosome 5. Prader-Willi syndrome is characterized by mental retardation, obesity, short stature, and small hands and feet. Angelman's syndrome is characterized by jerky movements and neurological symptoms. People with this syndrome also have an inability to control laughter, and may laugh inappropriately at odd moments. If a child inherits the defective chromosome from its father, the result is Prader-Willi syndrome. But if the child inherits the defective chromosome from its mother, the child will have Angelman's syndrome. Researchers believe that genes from the deleted region Figure 3. The four types of chromosome structure alterations. Illustration by Hans & Cassidy. Courtesy of Gale Group. function differently in offspring depending on whether the genes come from the mother or father, but they are not sure about the exact nature of these differences.

Another condition that depends on whether the defect is inherited from the mother or father is fragile X syndrome. In fragile X, an extra X chromosome hangs off the normal X by a thin "thread" of genetic material. The syndrome occurs in 1 out of 1,000 male births and 1 out of 2,000 female births. Males are affected more severely than females, and thus the syndrome is more pronounced if the child inherits the defect from its mother. To understand why this is so, remember that a male is XY and a female is XX. A male child receives a Y chromosome from the father and an X chromosome from the mother. A female child, however, can receive an X from either the mother or the father. Again, researchers believe this difference in fragile X symptoms between boys and girls stems from a difference in gene function that depends on whether they come from the mother or father.